Lipid-polymer hybrid nanoformulations combine the advantages of both polymeric nanoparticles and liposomes. Owing to the versatile chemistry of hydrophilic head moiety of phospholipid, it can further be modified with the desired units for a specific application, herein, polyethylene glycol as a stabilizer and tumor homing Lyp-1 peptide (sequence: CGNKRTRGC) as a ligand to target overexpressed p32 protein in tumor cells. This protein is a mitochondrial protein in normal cells, and not available to bind LyP-1, but its expression and the subcellular location is altered in many human carcinomas and experimental tumors. With this background, we engineered tumor homing lipid-polymer hybrid nanoparticle (LyP-1-HNP) to study its interaction with overexpressed cell surface protein p32 using osteosarcoma tumor model. The proposed LyP-1-HNP nanoconstruct is composed of PLGA, PEGylated phospholipid, and LyP-1-conjugated lipid, which was successfully employed to fabricate LyP-1-HNPs exhibiting the hydrodynamic size of 65± 7 nm with the negative zeta potential of −39.7 ± 2 mV. LyP-1-HNPs were found to be highly stable in physiological conditions over the period with PDI of 0.16 ±0.02. After understanding the colloidal properties of NPs, we evaluated in vitro safety and in vivo targeting properties. These hybrid nanoparticles showed excellent biocompatibility over the range of concentrations used and found to be accumulated in the tumor as revealed from in-vivo bio-imaging, which shows ~2.5 fold enhancement in tumor targeting as compared to its non-targeted counterparts in osteosarcoma xenograft. Considering the overexpression of p32 in many cancers, proposed nanoconstruct could hold promises in the treatment of wide range of tumors.

Interaction of tumor homing LyP-1 peptide designed as lipid-polymer hybrid nanoparticle with overexpressed cell surface protein p32 using osteosarcoma tumor model

2019 Spring National Meeting

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